Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality. Of the many potential predisposing factors, sepsis and pneumonia represent the two main causes of ARDS. In spite of an increase in survival in recent years mortality in patients with ARDS is still estimated around 30 to 40%. In this context, development of effective preventive strategies in patients at high risk of development of ARDS is of paramount importance. Unfortunately, the results of studies evaluating prophylactic regimens for ARDS have been mostly disappointing.

The gaseous molecule carbon monoxide (CO) has been traditionally viewed as a toxic metabolic and industrial waste. However, recent studies have demonstrated an important physiologic role of CO in many biological systems. Specifically, strong anti-inflammatory, anti-oxidant and anti-thrombotic effects of CO gas administration and heme oxygenase activation (the enzyme that generates endogenous CO gas) have been demonstrated in several animal models.

Previous studies conducted in our department have demonstrated that bronchoscopic instillation of endotoxin (LPS) in healthy volunteers elicits a compartmentalized pulmonary inflammatory response, serving as an excellent model to evaluate interventions directed towards suppression of lung inflammation at its earliest stages.

In the current single blinded, randomized, placebo controlled study, we are planning to evaluate the effects of inhaled carbon monoxide on local pulmonary inflammatory responses following endotoxin administration. Healthy subjects will undergo local endotoxin instillation, breathe CO or room air through a mask for 6 hours, and then a repeat bronchoscopy with lavage will be done at 6 hours to assess the ability of CO to suppress local inflammation in the lung.

Treatment or Intervention	Phase
Drug: Endotoxin  Drug: Carbon Monoxide	Phase I

Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality. Of the many potential predisposing factors, sepsis and pneumonia represent the two main causes of ARDS. In spite of an increase in survival in recent years mortality in patients with ARDS is still estimated around 30 to 40%. In this context, development of effective preventive strategies in patients at high risk of development of ARDS is of paramount importance. Unfortunately, the results of studies evaluating prophylactic regimens for ARDS have been mostly disappointing.

The gaseous molecule carbon monoxide (CO) has been traditionally viewed as a toxic metabolic and industrial waste. However, recent studies have demonstrated an important physiologic role of CO in many biological systems. Specifically, strong anti-inflammatory, anti-oxidant and anti-thrombotic effects of CO gas administration and heme oxygenase activation (the enzyme that generates endogenous CO gas) have been demonstrated in several animal models.

Previous studies conducted in our department have demonstrated that bronchoscopic instillation of endotoxin (LPS) in healthy volunteers elicits a compartmentalized pulmonary inflammatory response, serving as an excellent model to evaluate interventions directed towards suppression of lung inflammation at its earliest stages.

In the current single blinded, randomized, placebo controlled study, we are planning to evaluate the effects of inhaled carbon monoxide on local pulmonary inflammatory responses following endotoxin administration. Healthy subjects will undergo local endotoxin instillation, breathe CO or room air through a mask for 6 hours, and then a repeat bronchoscopy with lavage will be done at 6 hours to assess the ability of CO to suppress local inflammation in the lung.

Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

INCLUSION CRITERIA:
All volunteer subjects, employees and non-employees, must be 18 to 40 years of age and must be able to provide informed, written consent for participation in this study.
Normal screening examination including:
Medical history and physical examination, nonsmoker, no concurrent medications including aspirin or nonsteroidal anti-inflammatory drugs, no active medical problems.
Complete blood count with differential and platelet counts.
Serum chemistries including creatinine, blood urea nitrogen, glucose, liver enzymes and function tests, electrolytes, prothrombin time, partial thromboplastin time, carboxyhemoglobin measured by venous co-oxymetry.
Urinanalysis.
Female subjects must have negative urine pregnancy test within one week of participation (this will be repeated immediately prior to beginning the screening procedures due to radiation exposure from the chest x-ray).
Electrocardiogram.
Chest radiograph.
Sexually active females not using contraceptive methods will be instructed to abstain from sexual activity or use barrier contraception methods from the time of last negative pregnancy test to 24 hours after completion of the study.
EXCLUSION CRITERIA:
Active tobacco use.
Baseline caroxyhemoglobin greater than 2%.
Pregnancy.
Lactation.
Medical history of recent clinically significant asthma.
Allergy to both sulfa- and penicillin-based drugs.

Maryland
      National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  050012; 05-DK-0012
Record last reviewed:  May 4, 2004
Last Updated:  May 4, 2004
Record first received:  October 16, 2004
ClinicalTrials.gov Identifier:  NCT00094406
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-08